Normal aging is associated with reduced circulating levels of GH, IGF-1 and sex steroid hormones; decreased muscle mass; and increased total and intra-abdominal fat. Treatment with recombinant human GH (rhGH) or sex steroids improves body composition in some older persons, yet the effects of such hormonal treatment on various physiological functions remain to be defined. We are now conducting a placebo-controlled, double-masked study in a group of healthy, ambulatory, community-dwelling persons beyond 65 years of age, with low IGF-1 and sex steroid levels, to determine whether 6-months of administration of rhGH, sex steroid hormones (estrogen/progestin in women and testosterone in men), or rhGH plus sex steroids will increase or improve skeletal muscle mass, strength, and total body protein synthesis; decrease total and abdominal fat; and improve aerobic capacity and cardiovascular function, as well as selected endocrine, metabolic, immunological, dermatological, and psychobehavioral functions. We are also using PCR techniques to assess mRNAs for GH and IGF-1 receptors, IGF-I and IGF-BP's in skeletal muscle biopsies; and their relationships with certain physiological outcomes . Should this study reveal beneficial effects of hormone replacement, we plan to conduct longer-term investigations to examine the interaction of hormone treatment with other interventions , and their effects on functional status measurements, in other elderly populations. As of 11/30/96, we had entered 43 women and 53 men into the study, of whom 74 had finished, 16 were active, and 6 had dropped out. There have been no major adverse side effects. To achieve adquate numbers of subjects in each treatment group, we have received a 6th year extension, with carryover funding, through 6/30/98.